Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly.
Ferreira IATM., Lee CYC., Foster WS., Abdullahi A., Dratva LM., Tuong ZK., Stewart BJ., Ferdinand JR., Guillaume SM., Potts MOP., Perera M., Krishna BA., Peñalver A., Cabantous M., Kemp SA., Ceron-Gutierrez L., Ebrahimi S., CITIID-NIHR BioResource COVID-19 Collaboration None., Lyons P., Smith KGC., Bradley J., Collier DA., McCoy LE., van der Klaauw A., Thaventhiran JED., Farooqi IS., Teichmann SA., MacAry PA., Doffinger R., Wills MR., Linterman MA., Clatworthy MR., Gupta RK.
Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here, we show that individuals 70 years or older (median age 73, range 70-75) who received a primary two-dose schedule with AZD1222 and booster third dose with mRNA vaccine achieve significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared with those younger than 70 (median age 66, range 54-69) at 1 month post booster. Impaired neutralization potency and breadth post third dose in the elderly is associated with circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. However, when considering individuals who received three doses of mRNA vaccine, we did not observe differences in neutralization or enrichment in atypical B cells. This work highlights the finding that AdV and mRNA COVID-19 vaccine formats differentially instruct the memory B cell response.